1. Field of the Invention
The present invention relates, in general, to AAMP-1, and to a peptide derived from the amino-terminal region of AAMP, P189. In particular, the present invention relates to a DNA segment encoding AAMP-1, P189 or fragments thereof; polypeptides encoded by the DNA segments; recombinant DNA molecules containing the DNA segments; cells containing the recombinant DNA molecule; a method of producing AAMP-1, P189 or fragments thereof; antibodies specific to AAMP-1; and a method of measuring the amount of AAMP-1 in a sample. The present invention further relates to methods of using AAMP, P189 or fragments thereof in promoting cell-cell or cell-substrate adhesion, wound healing in patients, prosthetic acceptance, concentrating heparin in tissues, and inhibiting metastases and invasion of malignant cells.
2. Background Information
The major histocompatibility complex class II proteins have recently been found to contain local homologies to the HIV-1 envelope protein (H. Golding et al., J. Exp. Med. 167, 914 (1988); H. Golding et al., J. Clin. Invest. 83, 1430 (1989); J. A. T. Young, Nature 332, 215 (1988)). Such homologous regions may serve as targets for antibodies generated to HIV-1 proteins and thus compromise the immune system in AIDS. Golding et al. (J. Exp. Med. 167, 914 (1988)) have identified a common epitope located in the carboxy terminus of the HIV-1 gp4l-envelope protein and the amino terminal portion of the beta chain of all human HLA class II antigens. Although the epitope is small, 5 consecutive identities or similarities, they found that it is an effective example of "molecular mimicry" in that monoclonal antibodies raised against synthetic peptides from each protein react interchangeably with native HIV-1 envelope and MHC class II molecules. One third of HIV-1 positive individuals were shown to have serum antibodies directed against peptides derived from HIV-1 envelope protein, the homologous peptide from the MHC class II molecules, and native MHC class II molecules (H. Golding et al. J. Exp. Med. 167, 914 (1988)). Two other regions of the HLA class II beta chain and another immune related protein, interleukin-2, also show limited homology to HIV-1 (J. A. T. Young, Nature 333:215 (1988); M. A. Vega et al. Nature 345:26 (1990); W. E. Reiher III, et al. Proc. Natl. Acad. Sci. USA 83:9188 (1986)). An important consideration in HIV-1 vaccine development is the potential existence of additional host cell surface proteins with homologies to HIV-1 that may cross-react with antibodies directed against its peptides.
Certain adhesive molecules are known to carry out cell-cell and cell-substrate interactions which play a central role in development, differentiation, immune functions, wound healing, malignant transformation, and tumor invasion metastasis. They provide structural patterns in tissue architecture, participate in transmembrane links between the cytoskeleton and the extracellular matrix, serve as directional guides for migrating cells, participate in signal transduction, provide strong adhesion that may inhibit cell motility, or alternatively, weak and/or reversible adhesion that provides traction in cell motility (Edelman, G. M. Ann. Rev. Cell Biol. 2:81-116 (1986); Edelman et al. Ann. Rev. Biochem. 60:155-90 (1991); Edelman, G. M., Dev. Dynamics 193:2-10 (1992); Behrens, J., et al., Sem Cell Biol. 3:169-78 (1992).
Members of the Immunoglobulin superfamily are known to exhibit diverse binding properties, and include many adhesive proteins. Modulation of such adhesive proteins has been shown to play stimulatory or inhibitory roles in normal and tumor cell migration via alterations in intercellular adhesion, cell to substratum adhesion, and adherence of tumor cells and leukocytes to endothelial cells (Buck, C. A., Sem. Cell Biol. 3:179-88 (1992); Shevach, E. M. Immunophysiology, The Role of Cells and Cytokines in Immunity and Inflamation (Oppenheim, J. J., and Shevach, E. M., eds.) pp.104-28, Oxford University Press, New York). Furthermore, heparin and hyaluronan, two glycosaminoglycans, are known to be involved with the binding mechanisms of some of these adhesive proteins, such as Neural Cell Adhesion Molecule (NCAM), and the Cluster Differentiation (CD) proteins, CD4 and CD44. See, e.g., Buck, C. A., Sem. Cell Biol. 3:179-88 (1992); Cole, G. J. et al., Nature 320:445-7 (1986); Cole, G. J. et al., Neuron 2:1157-65 (1989); Reyes et al., Cell Regul. 1:567-76 (1990); Arufo et al., Cell 61:1303-13 (1990); Miyake et al., J. Exp. Med. 172:69-75 (1990); and Lederman, S. et al., J. Immunol. 143:1149-54 (1989).
The use of heparin binding proteins and peptides to promote heparin binding to synthetic substrates, cell adhesion to culture substrata, implant acceptance, and wound healing, as well as their use in inhibiting tumor metastasis and malignant cell invasion, has been previously described. (U.S. Pat. No. 5,081,031 to Furcht et al., U.S. Pat. No. 5,152,784, to Tsilibary et al., U.S. Pat. No. 5,120,828, to Charonis).